Our long-term goal is to understand at the cellular and molecular level the pathophysiology in hippocampal circuitry that is responsible for epileptiform seizures. CA3 pyramidal cell activity is controlled in part by the mossy fiber input from dentate granule cells, which in turn is regulated by the activity of local GABAergic neurons including dentate granule cells, which in turn is regulated by the activity of local GABAergic neurons including dentate basket cells. This project seeks to understand the ways in which dentate basket cell excitability is controlled, and to understand the functional consequences of glutamate receptor remodelling after repeated seizures. our major goals include: 1. To identify the cells of origin of monosynaptic and polysynaptic pathways from CA3 to dentate basket cells, and to characterize the synaptic modulation of these pathways. 2. To determine how seizures an brief hypoxic episodes modify the strength of excitatory inputs to dentate basket cells. 3. To determine whether long-term changes in the properties of excitatory inputs to basket cells occur following repeated seizures in pilocarpine- treated rats. 4. To determine whether down-regulation of GluR2 mRNA in CA3 pyramidal neurons in pilocarpine-treated rates produces functional changes in AMPA receptor permeation properties. Dual recordings in hippocampal slices from dentate basket cells and CA3 pyramidal cells will be used to study the CA3-dentate pathway(s) during the transition from normal to high-potassium burst-firing, during and after hypoxia and following the circuitry rearrangements induced by pilocarpine. Single cell PCR will be combined with patch clamp recordings from freshly dissociated pyramidal neurons to examine the permeation properties of AMPA receptors and the glutamate receptor mRNA content of individual pyramidal neurons from normal and pilocarpine-treated rates. These experiments should provide new information about tahe behavior of excitatory inputs to dentate basket neurons in several hyperexcitable conditions, including a test of the dormant basket cell hypothesis, and will determine the functional consequences of adjustments in glutamate receptors following prolonged seizures.